In:
PLOS Biology, Public Library of Science (PLoS), Vol. 22, No. 5 ( 2024-5-7), p. e3002299-
Abstract:
Activation of immune cells requires the remodeling of cell metabolism in order to support immune function. We study these metabolic changes through the infection of Drosophila larvae by parasitoid wasp. The parasitoid egg is neutralized by differentiating lamellocytes, which encapsulate the egg. A melanization cascade is initiated, producing toxic molecules to destroy the egg while the capsule also protects the host from the toxic reaction. We combined transcriptomics and metabolomics, including 13 C-labeled glucose and trehalose tracing, as well as genetic manipulation of sugar metabolism to study changes in metabolism, specifically in Drosophila hemocytes. We found that hemocytes increase the expression of several carbohydrate transporters and accordingly uptake more sugar during infection. These carbohydrates are metabolized by increased glycolysis, associated with lactate production, and cyclic pentose phosphate pathway (PPP), in which glucose-6-phosphate is re-oxidized to maximize NADPH yield. Oxidative PPP is required for lamellocyte differentiation and resistance, as is systemic trehalose metabolism. In addition, fully differentiated lamellocytes use a cytoplasmic form of trehalase to cleave trehalose to glucose and fuel cyclic PPP. Intracellular trehalose metabolism is not required for lamellocyte differentiation, but its down-regulation elevates levels of reactive oxygen species, associated with increased resistance and reduced fitness. Our results suggest that sugar metabolism, and specifically cyclic PPP, within immune cells is important not only to fight infection but also to protect the host from its own immune response and for ensuring fitness of the survivor.
Type of Medium:
Online Resource
ISSN:
1545-7885
DOI:
10.1371/journal.pbio.3002299
DOI:
10.1371/journal.pbio.3002299.g001
DOI:
10.1371/journal.pbio.3002299.g002
DOI:
10.1371/journal.pbio.3002299.g003
DOI:
10.1371/journal.pbio.3002299.g004
DOI:
10.1371/journal.pbio.3002299.g005
DOI:
10.1371/journal.pbio.3002299.g006
DOI:
10.1371/journal.pbio.3002299.g007
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10.1371/journal.pbio.3002299.t001
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10.1371/journal.pbio.3002299.s001
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10.1371/journal.pbio.3002299.s002
DOI:
10.1371/journal.pbio.3002299.s003
DOI:
10.1371/journal.pbio.3002299.s004
DOI:
10.1371/journal.pbio.3002299.s005
DOI:
10.1371/journal.pbio.3002299.s006
DOI:
10.1371/journal.pbio.3002299.s007
DOI:
10.1371/journal.pbio.3002299.s008
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10.1371/journal.pbio.3002299.s009
DOI:
10.1371/journal.pbio.3002299.s010
DOI:
10.1371/journal.pbio.3002299.s011
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10.1371/journal.pbio.3002299.s012
DOI:
10.1371/journal.pbio.3002299.s013
DOI:
10.1371/journal.pbio.3002299.s014
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10.1371/journal.pbio.3002299.s015
DOI:
10.1371/journal.pbio.3002299.s016
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10.1371/journal.pbio.3002299.s017
DOI:
10.1371/journal.pbio.3002299.s018
DOI:
10.1371/journal.pbio.3002299.s019
DOI:
10.1371/journal.pbio.3002299.s020
DOI:
10.1371/journal.pbio.3002299.s021
DOI:
10.1371/journal.pbio.3002299.r001
DOI:
10.1371/journal.pbio.3002299.r002
DOI:
10.1371/journal.pbio.3002299.r003
DOI:
10.1371/journal.pbio.3002299.r004
DOI:
10.1371/journal.pbio.3002299.r005
DOI:
10.1371/journal.pbio.3002299.r006
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2024
detail.hit.zdb_id:
2126773-X
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